dbSNP rs9331949: CLU:c.*1072A>G (chr8-27597169-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001831.4(CLU):c.*1072A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0555 in 454,130 control chromosomes in the GnomAD database, including 1,365 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.049 ( 334 hom., cov: 32)

Exomes 𝑓: 0.059 ( 1031 hom. )

Consequence

CLU
NM_001831.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.278

Publications

20 publications found

Variant links:

Genes affected

CLU (HGNC:2095): (clusterin) The protein encoded by this gene is a secreted chaperone that can under some stress conditions also be found in the cell cytosol. It has been suggested to be involved in several basic biological events such as cell death, tumor progression, and neurodegenerative disorders. Alternate splicing results in both coding and non-coding variants.[provided by RefSeq, May 2011]

CLU links:

ENSG00000300853 (HGNC:):

ENSG00000300853 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CLU	NM_001831.4 link	c.*1072A>G	3_prime_UTR_variant	Exon 9 of 9	ENST00000316403.15	NP_001822.3	P10909-1
CLU	NR_038335.2 link	n.2677A>G	non_coding_transcript_exon_variant	Exon 9 of 9
CLU	NR_045494.1 link	n.2602A>G	non_coding_transcript_exon_variant	Exon 9 of 9
LOC124901919	XR_007060868.1 link	n.1500T>C	non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLU	ENST00000316403.15 link	c.*1072A>G		3_prime_UTR_variant	Exon 9 of 9	1	NM_001831.4	ENSP00000315130.10		P10909-1

Frequencies

GnomAD3 genomes

AF:

0.0494

AC:

7522

AN:

152158

Hom.:

334

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0620

Gnomad AMI

AF:

0.128

Gnomad AMR

AF:

0.0158

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.214

Gnomad SAS

AF:

0.138

Gnomad FIN

AF:

0.0754

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0268

Gnomad OTH

AF:

0.0407

GnomAD2 exomes

AF:

0.0617

AC:

8240

AN:

133564

AF XY:

0.0687

show subpopulations

Gnomad AFR exome

AF:

0.0702

Gnomad AMR exome

AF:

0.0107

Gnomad ASJ exome

AF:

0.0269

Gnomad EAS exome

AF:

0.206

Gnomad FIN exome

AF:

0.0703

Gnomad NFE exome

AF:

0.0279

Gnomad OTH exome

AF:

0.0370

GnomAD4 exome

AF:

0.0586

AC:

17676

AN:

301854

Hom.:

1031

Cov.:

AF XY:

0.0675

AC XY:

11619

AN XY:

172034

show subpopulations

African (AFR)

AF:

0.0707

AC:

605

AN:

8554

American (AMR)

AF:

0.0107

AC:

293

AN:

27274

Ashkenazi Jewish (ASJ)

AF:

0.0293

AC:

316

AN:

10786

East Asian (EAS)

AF:

0.207

AC:

1910

AN:

9210

South Asian (SAS)

AF:

0.141

AC:

8437

AN:

59650

European-Finnish (FIN)

AF:

0.0668

AC:

830

AN:

12424

Middle Eastern (MID)

AF:

0.0243

AC:

AN:

1150

European-Non Finnish (NFE)

AF:

0.0290

AC:

4607

AN:

158764

Other (OTH)

AF:

0.0463

AC:

650

AN:

14042

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

1370

2740

4110

5480

6850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0494

AC:

7522

AN:

152276

Hom.:

334

Cov.:

AF XY:

0.0533

AC XY:

3966

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.0620

AC:

2575

AN:

41560

American (AMR)

AF:

0.0158

AC:

242

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0280

AC:

AN:

3468

East Asian (EAS)

AF:

0.214

AC:

1108

AN:

5176

South Asian (SAS)

AF:

0.138

AC:

664

AN:

4818

European-Finnish (FIN)

AF:

0.0754

AC:

800

AN:

10614

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0268

AC:

1824

AN:

68028

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

353

706

1060

1413

1766

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0303

Hom.:

128

Bravo

AF:

0.0447

Asia WGS

AF:

0.156

AC:

541

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over